Background and purpose: Anatomical changes induce differences between planned and delivered dose. Adaptive radiotherapy (ART) may reduce these differences but the optimal implementation is... Show moreBackground and purpose: Anatomical changes induce differences between planned and delivered dose. Adaptive radiotherapy (ART) may reduce these differences but the optimal implementation is insufficiently clear. The aims of this study were to quantify the difference between planned and delivered dose in HNC patients, assess the consequential difference in normal tissue complication probability (Delta NTCP) and to explore the value of Delta NTCP as an objective selection strategy for ART.Materials and methods: For 52 patients, daily doses were accumulated to estimate the delivered dose. The difference from planned dose was analyzed for CTVs and 9 organs-at-risk (OAR). Delta NTCP was calculated for xerostomia, dysphagia, parotid gland dysfunction and tube feeding dependency at 6 months. ART was deemed necessary if Delta NTCP was >5%. The positive predicted value (PPV) was calculated for identification of ART-patients by clinical judgement, and Delta NTCP at fraction 10 and 15.Results: Delta NTCP >5% was seen five times for dysphagia and twice for the other toxicities. Only 5/9 patients with any Delta NTCP >5% clinically received ART, although ART had been done for 13/52 patients (PPV: 0.38). PPV was 0.86 and 0.75 for accumulated dose at fraction 10 and 15, respectively, using a Delta NTCP cut-off for the allocation of ART of 5%. Using other Delta NTCP cut-offs did not substantially improve PPV. With this cutoff the negative predictive value was 0.93 for Delta NTCP method of fraction 10 and fraction 15, and 0.90 for clinical judgement.Conclusion: To identify patients accurately for ART, NTCP calculations based on the dose differences between planned and delivered dose at fraction 10 are superior to clinical judgement. (C) 2019 Published by Elsevier B.V. Show less
Widder, J.; Schaaf, A. van der; Lambin, P.; Marijnen, C.A.M.; Pignol, J.P.; Rasch, C.R.; ... ; Langendijk, J.A. 2016
Background. The purpose of this study was to evaluate the long-term results of primary radiotherapy treatment for squamous cell carcinoma (SCC) of the nasal vestibule.Methods. Eighty-one patients... Show moreBackground. The purpose of this study was to evaluate the long-term results of primary radiotherapy treatment for squamous cell carcinoma (SCC) of the nasal vestibule.Methods. Eighty-one patients were treated with external beam radiotherapy (EBRT) and/or interstitial radiotherapy (IRT) for a primary, localized, Wang classified SCC of the nasal vestibule.Results. Median follow-up was 38 months. T1 tumors were treated with IRT: we observed 1 local failure (at 13 months) among 48 patients (5-year local control rate of 97%). Most T2 tumors (20 of 26) were treated with EBRT. There were 8 local recurrences among 26 patients (5-year local control rate of 68%). For the T3 tumors (n = 7; all treated with EBRT), we observed local recurrence in 2 patients (5-year local control rate of 53%). The late-term side effects were relatively mild.Conclusion. Local primary radiotherapy (either IRT for T1 or EBRT for T2/3) is an adequate treatment for SCC of the nasal vestibule with little late sequelae. (C) 2015 Wiley Periodicals, Inc. Show less
Background. The radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) phase III trial compared intra-arterial (IA) to intravenous (IV) cisplatin-based chemoradiation... Show moreBackground. The radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) phase III trial compared intra-arterial (IA) to intravenous (IV) cisplatin-based chemoradiation for head and neck cancer. Long-term efficacy and toxicity are reported after a median follow-up of 7.5 years.Methods. Patients with inoperable squamous cell carcinoma (SCC) of the oropharynx, oral cavity, or hypopharynx, were randomized between radiotherapy (RT) + IA cisplatin 150 mg/m(2), followed by systemic rescue or RT + I. V. cisplatin 100 mg/m(2). RT consisted of 46 Gy to the affected and elective areas, followed by a boost of 24 Gy.Results. Among 237 patients, 57 recurred locally, 35 regionally, and 80 locoregionally. There were 32 second primary tumors, 65 distant metastases, and 154 deaths. Locoregional control and overall survival were not different between the treatment arms. Late dysphagia was worse in the I.V. arm (log-rank p=.014).Conclusion. IA cisplatin did not improve tumor control compared to I.V. administered cisplatin, despite the higher dose in IA delivery of the drug. (C) 2015 Wiley Periodicals, Inc. Show less
Longo, T.A.; Gopalakrishna, A.; Tsivian, M.; Noord, M. van; Rasch, C.R.; Inman, B.A.; Geijsen, E.D. 2016
Context: Bladder cancer therapy remains suboptimal as morbidity and mortality remain high amongst those with non-muscle-invasive and muscle-invasive disease. Regional hyperthermia therapy (RHT) is... Show moreContext: Bladder cancer therapy remains suboptimal as morbidity and mortality remain high amongst those with non-muscle-invasive and muscle-invasive disease. Regional hyperthermia therapy (RHT) is a promising adjunctive therapy being tested in multiple clinical contexts.Objective: The aim of this study was to systematically review the literature on the efficacy and toxicity of RHT.Evidence acquisition: This systematic review was registered with the PROSPERO database (Registration number: CRD42015025780) and was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We queried PubMed, EMBASE, and Cochrane libraries. Two reviewers reviewed abstracts independently and a third reviewer arbitrated disagreements. The last search was performed on 28 August 2015. A descriptive analysis was performed and quality assessment was conducted using the Newcastle-Ottawa Quality Assessment Scale for observational studies, and the Cochrane Risk of Bias Assessment Tool for trials.Evidence synthesis: We identified 859 publications in the initial search, of which 24 met inclusion criteria for full-text review. Of these, we were able to obtain data on the outcomes of interest for 15 publications.Conclusions: The review underscores the limited nature of the evidence; definitive conclusions are elusive. However, the promising results of RHT in the setting of intravesical chemotherapy, chemotherapy and radiotherapy show a trend towards legitimate efficacy. Show less
Geijsen, E.D.; Reijke, T.M. de; Koning, C.C.; Vording, P.J.Z.V.S.; Rosette, J.J. de la; Rasch, C.R.; ... ; Crezee, J. 2015
Purpose: Despite intravesical therapy with immunotherapy or chemotherapy intermediate and high risk nonmuscle invasive bladder cancer is associated with a high risk of recurrence and progression to... Show morePurpose: Despite intravesical therapy with immunotherapy or chemotherapy intermediate and high risk nonmuscle invasive bladder cancer is associated with a high risk of recurrence and progression to muscle invasive bladder carcinoma. While intravesical hyperthermia combined with mitomycin C has proved effective to treat nonmuscle invasive bladder cancer, there is less experience with invasive regional 70 MHz hyperthermia and mitomycin C. Therefore, we examined the safety and feasibility of this treatment combination for intermediate and high risk nonmuscle invasive bladder cancer.Materials and Methods: Between 2009 and 2011, 20 patients with intermediate and high risk nonmuscle invasive bladder cancer were treated with intravesical mitomycin C (40 mg) combined with regional hyperthermia. Treatment consisted of 6 weekly sessions followed by a maintenance period of 1 year with 1 hyperthermia-mitomycin C session every 3 months. Regional hyperthermia was administered using a 70 MHz phased array system with 4 antennas. Toxicity was scored using CTC (Common Toxicity Criteria) 3.0.Results: The records of 18 of 20 patients could be analyzed. Median followup was 46 months. Of the 18 patients 15 (83%) completed the induction period of 6 treatments. Four patients (22%) discontinued treatment because of physical complaints without exceeding grade 2 toxicity. Toxicity scored according to CTC 3.0 was limited to grade 1 in 43% of cases and grade 2 in 14%. Mean T90 and T50 bladder temperatures were 40.6C and 41.6C, respectively. The 24-month recurrence-free survival rate was 78%.Conclusions: Treatment with regional hyperthermia combined with mitomycin C in patients with intermediate and high risk nonmuscle invasive bladder cancer is feasible with low toxicity and excellent bladder temperatures. Show less
Boer, P. de; Adam, J.A.; Buist, M.R.; Vijver, M.J. van de; Rasch, C.R.; Stoker, J.; ... ; Stalpers, L.J.A. 2013
Purpose: In patients with uterine cervical cancer, pretreatment recognition of uterine extension is crucial in treatment decision-making for fertility-sparing surgery and for target delineation in... Show morePurpose: In patients with uterine cervical cancer, pretreatment recognition of uterine extension is crucial in treatment decision-making for fertility-sparing surgery and for target delineation in radiotherapy. Although MRI is generally considered the most reliable method, its value for detecting involvement of the uterine internal os is unclear.Methods: Medline, Embase and Cochrane databases were systematically searched (January 1997-December 2012) for MRI studies that measured the accuracy of involvement of the uterine internal os compared to histopathology as reference standard in patients with uterine cervical cancer. Data were assessed using the QUADAS tool. Accuracy concerned either involvement (yes/no) of the uterine internal os, or measuring invasion distance toward the uterine corpus.Results: Two retrospective and two prospective studies described 366 patients diagnosed with uterine cervical cancer FIGO stage IIB or below, in whom 64 (17%) had uterine internal os involvement. For three studies the summary estimates of specificity, sensitivity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were 91%, 97%, 99%, 79% and 95%, respectively; one study had an area under the curve (AUC) of 0.8.Conclusion: MRI has a high level of accuracy; however, data are limited and for validation a large prospective study is needed that compares actual measurements on MRI with histopathological examination. (C) 2013 Elsevier Ireland Ltd. All rights reserved. Show less
Dinkla, A.M.; Pieters, B.R.; Koedooder, K.; Wieringen, N. van; Laarse, R. van der; Grient, J.N. van der; ... ; Bel, A. 2013
Background. Due to improved visibility on MRI, contouring of the prostate is improved compared to CT. The aim of this study was to quantify the benefits of using MRI for treatment planning as... Show moreBackground. Due to improved visibility on MRI, contouring of the prostate is improved compared to CT. The aim of this study was to quantify the benefits of using MRI for treatment planning as compared to CT-based planning for temporary implant prostate brachytherapy. Material and methods. CT and MRI image data of 13 patients were used to delineate the prostate and organs at risk (OARs) and to reconstruct the implanted catheters (typically 12). An experienced treatment planner created plans on the CT-based structure sets (CT-plan) and on the MRI-based structure sets (MRI-plan). Then, active dwell-positions and weights of the CT-plans were transferred to the MRI-based structure sets (CT-plan(MRI-contours)) and resulting dosimetric parameters and tumour control probabilities (TCPs) were studied. Results. For the CT-plan(MRI-contours) a statistically significant lower target coverage was detected: mean V-100 was 95.1% as opposed to 98.3% for the original plans (p < 0.01). Planning on CT caused cold-spots that influence the TCP. MRI-based planning improved the TCPs by 6-10%, depending on the parameters of the radiobiological model used for TCP calculation. Basing the treatment plan on either CT- or MRI-delineations does not influence plan quality. Conclusion. Evaluation of CT-based treatment planning by transferring the plan to MRI reveals underdosage of the prostate, especially at the base side. Planning on MRI can prevent cold-spots in the tumour and improves the TCP. Show less
Background. Predictive models for swallowing dysfunction were developed previously and showed the potential of improved intensity-modulated radiotherapy to reduce the risk of swallowing dysfunction... Show moreBackground. Predictive models for swallowing dysfunction were developed previously and showed the potential of improved intensity-modulated radiotherapy to reduce the risk of swallowing dysfunction. Still the risk is high. The aim of this study was to determine the potential of swallowing-sparing (SW) intensity-modulated proton therapy (IMPT) in head and neck cancer (HNC) for reducing the risk of swallowing dysfunction relative to currently used photon therapy. Material and methods. Twenty-five patients with oropharyngeal (n = 21) and hypopharyngeal (n = 4) cancer received primary radiotherapy, including bilateral neck irradiation, using standard (ST) intensity-modulated photon therapy (IMRT). Prophylactic (54 Gy) and therapeutic (70 Gy) target volumes were defined. The dose to the parotid and submandibular glands was reduced as much as possible. Four additional radiotherapy plans were created for each patient: SW-IMRT, ST-IMPT, 3-beam SW-IMPT (3B-SW-IMPT) and 7-beam SW-IMPT (7B-SW-IMPT). All plans were optimized similarly, with additional attempts to spare the swallowing organs at risk (SWOARs) in the SW plans. Probabilities of swallowing dysfunction were calculated with recently developed predictive models. Results. All plans complied with standard HNC radiotherapy objectives. The mean parotid gland doses were similar for the ST and SW photon plans, but clearly lower in all IMPT plans (ipsilateral parotid gland ST-IMRT: 46 Gy, 7B-SW-IMPT: 29 Gy). The mean dose in the SWOARs was lowest with SW-IMPT, in particular with 7B-SW-IMPT (supraglottic larynx ST-IMRT: 60 Gy, 7B-SW-IMPT: 40 Gy). The observed dose reductions to the SWOARs translated into substantial overall reductions in normal tissue complication risks for different swallowing dysfunction endpoints. Compared with ST-IMRT, the risk of physician-rated grade 2-4 swallowing dysfunction was reduced on average by 8.8% (95% CI 6.5-11.1%) with SW-IMRT, and by 17.2% (95% CI: 12.7-21.7%) with 7B-SW-IMPT. Conclusion. SWOAR-sparing with proton therapy has the potential to substantially reduce the risk of swallowing dysfunction compared to similar treatment with photons. Show less
Knegjens, J.L.; Hauptmann, M.; Pameijer, F.A.; Balm, A.J.; Hoebers, F.J.; Bois, J.A. de; ... ; Rasch, C.R. 2011
Background. Tumor volume is an important predictor of outcome in radiotherapy alone. Its significance in concomitant chemoradiation (CCRT) is much less clear. We analyzed the prognostic value of... Show moreBackground. Tumor volume is an important predictor of outcome in radiotherapy alone. Its significance in concomitant chemoradiation (CCRT) is much less clear. We analyzed the prognostic value of primary tumor volume for advanced head and neck squamous cell carcinoma (HNSCC) treated with CCRT.Methods. Three hundred sixty patients treated with definitive CCRT for advanced HNSCC were selected. The pretreatment MRI or CT scan was used to calculate the primary tumor volume. Median follow-up was 19.8 months.Results. The average primary tumor volume was 37.0 cm(3) (range, 2.1-182.7 cm(3); median, 28.7 cm(3)). Multivariate analysis showed a significant effect of tumor volume on local control. The hazard ratio for a local recurrence increased by 14% per 10 cm(3) volume increase (95% CI, 8% to 21%). There was no significant independent effect of T and N status on local control.Conclusion. For advanced HNSCC, tumor volume is more powerful for predicting outcome after CCRT than TNM status. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 375-382, 2011 Show less
Jong, M.C. de; Pramana, J.; Wal, J.E. van der; Lacko, M.; Peutz-Kootstra, C.J.; Jong, J.M. de; ... ; Begg, A.C. 2010
Purpose: To find molecular markers from expression profiling data to predict recurrence of laryngeal cancer after radiotherapy. Experimental Design: We generated gene expression data on pre... Show morePurpose: To find molecular markers from expression profiling data to predict recurrence of laryngeal cancer after radiotherapy. Experimental Design: We generated gene expression data on pre-treatment biopsies from 52 larynx cancer patients. Patients developing a local recurrence were matched for T-stage, subsite, treatment, gender and age with non-recurrence patients. Candidate genes were then tested by immunohistochemistry on tumor material from a second series of 76 patients. Both series comprised early stage cancer treated with radiotherapy alone. Finally, gene expression data of eight larynx cancer cell lines with known radiosensitivity were analyzed. Results: Nineteen patients with a local recurrence were matched with 33 controls. Gene sets for hypoxia, proliferation and intrinsic radiosensitivity did not correlate with recurrence, whereas expression of the putative stem cell marker CD44 did. In a supervised analysis, probes for all three splice variants of CD44 on the array appeared in the top 10 most significantly correlated with local recurrence. Immunohistochemical analysis of CD44 expression on the independent validation series confirmed CD44's predictive potential. In 8 larynx cancer cell lines, CD44 gene expression did not correlate with intrinsic radiosensitivity although it did correlate significantly with plating efficiency, consistent with a relationship with stem cell content. Conclusions: CD44 was the only biological factor tested which significantly correlated with response to radiotherapy in early stage larynx cancer patients, both at the mRNA and protein levels. Further studies are needed to confirm this and to assess how general these findings are for other head and neck tumor stages and sites. Clin Cancer Res; 16(21); 5329-38. (C) 2010 AACR. Show less
